Instructions for Taklor tablets 25 mg No. 30
Composition
active ingredient: chlortalidone;
1 tablet contains chlorthalidone 25.0 mg;
Excipients: lactose monohydrate; microcrystalline cellulose; povidone; colloidal anhydrous silica; magnesium stearate; sodium starch glycolate (Type A).
Dosage form
Pills.
Main physicochemical properties: tablets from white or almost white to white with a yellowish tint, round in shape with a flat surface, with a bevel.
Pharmacotherapeutic group
Diuretics. Non-thiazide diuretics with moderate activity. Simple sulfonamides. Chlorthalidone. ATC code C03B A04.
Pharmacological properties
Pharmacodynamics
Chlorthalidone is a long-acting thiazide-like diuretic.
Thiazide and thiazide-like diuretics, including chlorthalidone, act primarily at the level of the distal renal tubules (distal convoluted tubule), inhibiting the reabsorption of Na and Cl, which can result in the excretion of approximately 15% of glomerularly filtered sodium, and increasing the reabsorption of calcium ions, which can lead to hypercalcemia. The increased influx of sodium ions and water in the cortical collecting duct and the increase in urine flow rate lead to increased secretion and excretion of potassium and hydrogen ions.
High doses of chlorthalidone may cause increased bicarbonate excretion due to inhibition of carbonic anhydrase, which alkalizes the urine.
Acidosis or alkalosis have no significant effect on the saluretic or diuretic effects of chlorthalidone. With prolonged therapy with chlorthalidone, renal calcium excretion is reduced, which may lead to hypercalcemia.
The diuretic effect occurs 2–3 hours after administration, reaches a maximum after 4–24 hours, and can persist for 2–3 days.
Chlorthalidone-induced diuresis leads to a decrease in plasma volume, cardiac output, and systemic blood pressure. In patients with hypertension, chlorthalidone slowly reduces blood pressure. The antihypertensive effect of chlorthalidone occurs at the beginning of therapy due to a decrease in extracellular volume and, as a result, a decrease in peripheral resistance. With prolonged treatment, the extracellular volume normalizes and the antihypertensive efficacy is maintained, which may be due to a later decrease in the concentration of sodium in the vascular walls and, thus, a decrease in sensitivity to norepinephrine.
Chlorthalidone has an antidiuretic effect in patients with nephrogenic diabetes insipidus. The mechanism of action is not yet clear.
Chlorthalidone is ineffective in patients with severe renal impairment (creatinine clearance below 30 ml/min and/or serum creatinine above 1.8 mg/100 ml).
Pharmacokinetics
Absorption
Chlorthalidone is absorbed from the gastrointestinal tract relatively slowly (t50 of absorption is approximately 2.6 hours). The bioavailability of an oral dose of 50 mg of chlorthalidone is approximately 64%, with peak blood concentrations occurring 8–12 hours after administration.
Distribution
The binding of chlorthalidone to plasma proteins is approximately 75%, the volume of distribution is 4 l/kg. Only a small part of free chlorthalidone is found in the blood due to the high accumulation in erythrocytes and binding to plasma proteins.
Metabolism and excretion
Within 120 hours after administration, approximately 70% of the dose is excreted in the urine and feces, mainly unchanged. Hepatic metabolism and biliary excretion are only a minor part of the elimination pathway. The half-life is on average 50 hours.
Special patient groups
The elimination of chlorthalidone is slowed in elderly patients compared to healthy young volunteers, although absorption is similar.
Chlorthalidone crosses the placental barrier and enters breast milk.
Indication
Treatment
arterial hypertension; cardiac, hepatic and nephrogenic edema; chronic heart failure; nephrogenic diabetes insipidus, when other therapeutic measures are excluded.
Contraindication
Known hypersensitivity to chlorthalidone, other thiazides and sulfonamide derivatives (possibility of cross-reactions, use with caution in patients with bronchial asthma) or to any of the components of the drug; anuria (diuresis less than 100 ml/day); severe renal failure (significantly reduced diuresis, creatinine clearance ml/min and/or serum creatinine more than 1.8 mg/100 ml); glomerulonephritis; severe hepatic failure (hepatic precoma and coma); hypercalcemia; hypokalemia resistant to therapy or conditions with increased potassium loss; severe hyponatremia; symptomatic hyperuricemia.
Interaction with other medicinal products and other types of interactions
Not recommended combinations:
Lithium
Concomitant use of chlorthalidone and lithium leads to increased cardio- and neurotoxic effects of lithium due to reduced lithium excretion. If diuretic therapy is essential, careful monitoring of lithium blood levels and dose adjustment are required.
Combinations requiring special precautions:
Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol); Certain antipsychotics: phenothiazines (e.g. chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (e.g. amisulpiride, sulpiride, sultopride, tiapride), butyrophenones (e.g. droperidol, haloperidol); Others: bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamine IV.
When these drugs are administered concomitantly with chlorthalidone, especially in the presence of hypokalemia, there is an increased risk of ventricular arrhythmias, especially torsade de pointes. Before using the above drugs together with chlorthalidone, serum potassium levels should be determined and corrected. ECG monitoring and plasma electrolyte levels should be performed regularly. In the presence of hypokalemia, it is recommended to use drugs that do not cause torsade de pointes.
ACE inhibitors (e.g., captopril, enalapril)
Concomitant use of chlorthalidone and ACE inhibitors (e.g. captopril, enalapril), especially at the beginning of treatment, may result in a significant decrease in blood pressure and deterioration of renal function. Therefore, diuretic therapy should be discontinued 2-3 days before starting treatment with an ACE inhibitor to reduce the likelihood of hypotension at the beginning of therapy.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. indomethacin, acetylsalicylic acid), including COX-2 inhibitors, salicylates
NSAIDs (e.g. indomethacin, acetylsalicylic acid), including COX-2 inhibitors and salicylates, may reduce the antihypertensive and diuretic effects of chlorthalidone. When using high doses of salicylates, the toxic effects of salicylates on the central nervous system may be enhanced. If patients develop hypovolemia during chlorthalidone therapy, the simultaneous use of NSAIDs may provoke acute renal failure.
Kaliuretic diuretics (e.g., furosemide), glucocorticoids, adrenocorticotropic hormone (ACTH), carbenoxolone, penicillin G, salicylates, stimulant laxatives, amphotericin B (parenteral)
Concomitant use of chlorthalidone and these medicinal products may lead to electrolyte imbalance, in particular increased potassium loss. This is particularly important in the case of concomitant treatment with cardiac glycosides. It is necessary to regularly check and, if necessary, correct the level of potassium in the blood plasma.
Other diuretics, other antihypertensive agents (e.g. beta-blockers, calcium channel blockers, ACE inhibitors, vasodilators, methyldopa, guanethidine), nitrates, barbiturates, phenothiazines, tricyclic antidepressants, alcohol
The hypotensive effects of chlorthalidone may be enhanced by the use of these drugs or alcohol.
Cardiac glycosides
If hypokalemia and/or hypomagnesemia develop during the simultaneous use of chlorthalidone with cardiac glycosides, the sensitivity of the myocardium to cardiac glycosides increases, and the effects and side effects of cardiac glycosides are accordingly enhanced.
Interactions with the following medications are also possible:
Insulin, oral antidiabetic agents, uric acid lowering agents, sympathomimetics (noradrenaline [norepinephrine], adrenaline [epinephrine])
The effects of these drugs may be reduced when used concomitantly with chlorthalidone. Dosage adjustments of insulin and oral antidiabetic drugs may be required.
Non-depolarizing (curare-like) muscle relaxants (e.g., tubocurarine)
The effect of curare-like muscle relaxants may be enhanced or prolonged by chlorthalidone. If chlorthalidone cannot be discontinued prior to the use of curare-like muscle relaxants, the anaesthetist should be informed of the chlorthalidone treatment.
Cytostatics (e.g. cyclophosphamide, fluorouracil, methotrexate)
Chlorthalidone may reduce the renal excretion of cytostatics (e.g. cyclophosphamide, fluorouracil, methotrexate). With simultaneous use of cytostatics, increased bone marrow toxicity (especially the development of granulocytopenia) can be expected.
Cholestyramine, colestipol
Concomitant use of cholestyramine or colestipol reduces the absorption of chlorthalidone.
Therefore, Taclor should be taken at least one hour before or 4-6 hours after taking these medications.
Calcium salts, vitamin D
Concomitant use of chlorthalidone and calcium or vitamin D may increase serum calcium levels due to decreased excretion.
Allopurinol
Tacrolimus may potentiate hypersensitivity reactions to allopurinol.
Amantadine
Chlorthalidone may increase the risk of side effects of amantadine.
Beta-blockers, diazoxide
There is an increased risk of hyperglycemia with the simultaneous use of Tacrolimus and beta-blockers or diazoxide.
Cyclosporine
Concomitant use of cyclosporine may increase the risk of hyperuricemia and gouty complications.
Anticholinergics (e.g., atropine, biperidine)
Application features
Kidney dysfunction
Taclor should be used with caution in patients with kidney disease.
In patients with mild to moderate renal impairment (creatinine clearance 30 - 60 ml/min and/or serum creatinine 1.1 - 1.8 mg/100 ml), the dosage should be adjusted according to therapeutic requirements and tolerability (see section 4.2).
In patients with severe renal insufficiency (creatinine clearance below 30 ml/min and/or serum creatinine above 1.8 mg/100 ml), thiazide diuretics and thiazide analogues, including chlorthalidone, lose their diuretic effect (see section "Contraindications").
Thiazide and thiazide-like diuretics, including chlorthalidone, may cause azotemia in patients with renal disease. Cumulative drug effects may occur in patients with impaired renal function. If renal failure progresses, as evidenced by an increase in total blood nitrogen without protein nitrogen, a decision should be made about the appropriateness of further treatment. Discontinuation of diuretic therapy should be considered.
Chronic diuretic abuse can lead to pseudo-Bartter syndrome, which is accompanied by the development of edema. Edema is a manifestation of increased renin levels, which leads to secondary hyperaldosteronism.
The hypotensive effect of ACE inhibitors is enhanced by drugs that increase plasma renin activity (diuretics). Therefore, diuretic therapy should be discontinued 2-3 days before treatment with an ACE inhibitor to reduce the possibility of hypotension at the beginning of therapy.
Liver dysfunction
Taclor should be used with caution in patients with impaired liver function or progressive liver disease, since even minor changes in fluid and electrolyte balance due to the effects of thiazide diuretics, especially in patients with cirrhosis, can precipitate hepatic coma (see section "Contraindications").
Metabolic and endocrine disorders
Patients with diabetes or gout need special attention.
Thiazide and thiazide-like diuretic therapy, including chlorthalidone, may affect glucose tolerance. Patients with diabetes mellitus may experience metabolic disturbances, which may require adjustment of the dose of insulin or oral hypoglycemic agents. Latent diabetes mellitus may become manifest during chlorthalidone therapy.
Blood uric acid levels may increase during treatment with chlorthalidone, but gout attacks rarely occur during long-term therapy.
In patients receiving long-term treatment with thiazide and thiazide-like diuretics, small and partially reversible increases in plasma total cholesterol, low-density lipoprotein (LDL) or triglycerides have been observed.
Electrolyte disturbances
During treatment with diuretics, serum electrolytes (especially potassium, sodium, calcium) should be determined at regular intervals.
Continuous monitoring of serum electrolytes is particularly important in elderly patients, patients with ascites due to cirrhosis of the liver, and patients with nephrogenic edema. In such conditions, Tacrolimus should be used only under close supervision and only in patients whose serum potassium levels are within normal limits and who do not show signs of dehydration.
Thiazide and thiazide-like diuretics, including chlorthalidone, may cause electrolyte disturbances (hypokalemia, hyponatremia, and hypochloraemic alkalosis). The first signs of electrolyte disturbances are dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular weakness, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may also increase myocardial sensitivity to the toxic effects of cardiac glycosides.
The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients with increased diuresis, in patients without adequate electrolyte intake and in patients treated with corticosteroids, ACTH, cardiac glycosides or laxatives (see section "Interaction with other medicinal products and other types of interactions"). Such patients require careful monitoring.
As with all thiazide and thiazide-like diuretics, chlorthalidone-induced potassium loss is dose-dependent and varies in individual patients. At a dose of 25 mg/day, the average decrease in serum potassium is 0.5 mmol/l. During long-term treatment, serum potassium should be measured at the start of treatment and then every 3-4 weeks. Thereafter, if there are no other factors affecting potassium levels (e.g. vomiting, diarrhoea, changes in renal function), serum potassium levels can be measured every 4-6 months.
The combination of chlorthalidone and potassium or potassium-sparing diuretics should not be used in patients receiving concomitant ACE inhibitors unless the combination is considered essential.
Dilutional hyponatremia may occur in patients with edema in hot weather. Chloride deficiency is usually mild and does not require treatment.
Thiazide and thiazide-like diuretics, including chlorthalidone, may reduce urinary calcium excretion and cause a transient and minor increase in serum calcium without known disturbances of calcium metabolism. Significant hypercalcemia may be a sign of latent hyperparathyroidism. Chlorthalidone should be discontinued before testing parathyroid function.
Thiazide and thiazide-like diuretics have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia.
Heart failure
In patients with severe heart failure, the absorption of chlorthalidone may be reduced.
Others
Hypersensitivity reactions may occur in patients with a history of allergy or bronchial asthma or without a significant allergic history.
Special precautions
During chlorthalidone therapy, serum electrolyte levels (especially potassium, sodium, calcium ions), creatinine and urea, serum lipids (cholesterol and triglycerides), uric acid and blood sugar should be regularly checked.
It is necessary to ensure that patients drink sufficient fluids during treatment with chlorthalidone and consume foods rich in potassium (bananas, vegetables, nuts) due to increased potassium losses.
Treatment of high blood pressure with Taclor requires regular medical check-ups.
Taclor therapy should be discontinued if:
treatment-resistant electrolyte imbalances; hypersensitivity reactions; severe gastrointestinal complaints; central nervous system disorders; pancreatitis; blood system disorders (anemia, leukopenia, thrombocytopenia); acute cholecystitis; vasculitis; worsening of existing myopia; serum creatinine levels above 1.8 mg/100 ml or creatinine clearance below 30 ml/min.
Use for unlawful purposes
The use of chlorthalidone may lead to positive doping control results. It is not possible to exclude negative consequences and serious health risks from the use of chlorthalidone as a doping agent.
Excipients
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
Due to the occurrence of various, individually determined reactions, a violation of the reaction rate is possible, which may lead to the inability to actively participate in traffic, drive machinery or work without stable support. This is especially pronounced at the beginning of treatment, when increasing the dose, in combination with other antihypertensive agents, when changing drugs and when taken simultaneously with alcohol.
Use during pregnancy or breastfeeding
Pregnancy
Chlorthalidone should not be used during pregnancy and lactation.
Chlorthalidone, like other diuretics, may reduce placental blood flow. Thiazides and thiazide analogues also enter the fetal circulation and may cause electrolyte imbalance. There have been reports of neonatal thrombocytopenia associated with the use of thiazide diuretics.
Breastfeeding period
Chlorthalidone passes into breast milk. Breastfeeding women should not take chlorthalidone or should refrain from breastfeeding.
Method of administration and doses
Dosage depends on the clinical picture and the patient's response to therapy. It is recommended to use the lowest effective dose. Gradual dose titration is recommended for patients with ischemic disease or cerebral atherosclerosis, as well as after a heart attack or hemorrhagic stroke. Chlorthalidone is taken orally with sufficient fluid (1 glass of water). If the doctor prescribes a single dose, then take it in the morning with breakfast or in the morning and evening in the case of a double dose. If necessary, the dose is increased no earlier than after 2-3 weeks.
The duration of use is prescribed by a doctor. Treatment is discontinued by gradually reducing the dose.
Use in adult patients:
Arterial hypertension
The initial dose is 12.5* -50 mg per day, the maintenance dose is 25-50 mg of chlorthalidone every other day.
Edema of specific origin and heart failure
The recommended initial dose is 50-100 mg per day, the maximum daily dose is 200 mg, the maintenance dose is 25-50 mg of chlorthalidone per day.
Nephrogenic diabetes insipidus
The initial dose is 100 mg 2 times a day, but with further therapy, the daily maintenance dose may be reduced to 50 mg per day.
Elderly patients and patients with renal impairment
In elderly patients and/or in patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min and/or serum creatinine 1.1-1.8 mg/dL), the dosage should be adjusted according to therapeutic requirements and tolerability. Thiazide and thiazide-like diuretics and thiazide analogues, including chlorthalidone, lose their diuretic effect at creatinine clearance <30 ml/min and/or serum creatinine above 1.8 mg/dL (see section 4.3).
Patients with liver dysfunction
The dose of chlorthalidone should be titrated accordingly in patients with hepatic impairment (see section 4.4). Tacrolimus should not be used in patients with severe hepatic impairment (see section 4.4).
Patients with heart failure
In patients with decompensated heart failure, chlorthalidone is practically not absorbed.
*Use chlorthalidone preparations in the appropriate dosage.
Children
Experience with the drug in the pediatric population is limited, therefore chlorthalidone should not be used in children.
Overdose
Symptoms of overdose
The clinical picture of acute or chronic overdose depends on the degree of fluid and electrolyte loss.
The following symptoms may occur:
Dizziness and weakness, nausea, drowsiness, muscle pain and muscle spasms (e.g., calf muscle cramps), headache, tachycardia, hypotension, orthostatic and electrolyte disturbances (hypokalemia and/or hyponatremia).
Dehydration and hypovolemia can cause hemoconcentration, seizures, drowsiness, lethargy, confusion, collapse, and acute renal failure.
Hypokalemia can cause fatigue, muscle weakness, paresthesia, paresis, apathy, flatulence and constipation or cardiac arrhythmia. Significant loss of potassium can cause paralytic ileus or loss of consciousness up to hypokalemic coma.
Treatment. If there are signs of overdose, treatment should be stopped immediately. In addition to general measures, vital signs should be monitored and, if necessary, corrected in intensive care. There is no specific antidote for chlorthalidone. If the patient is conscious, gastric lavage is necessary, and sorbents are prescribed to reduce absorption. According to clinical indications, intravenous administration of fluids and electrolytes, monitoring of blood pressure, water and electrolyte balance and metabolic functions may be required.
Adverse reactions
Adverse reactions were classified by system organ class and frequency of occurrence.
The frequency of adverse reactions is defined as follows:
very common (≥1/10); common (≥1/100 - <1/10); uncommon (≥1/1000 - <1/100); rare (≥1/10,000 - <1/1000); very rare (<1/10,000); frequency unknown (frequency cannot be estimated from the available data).
Blood and lymphatic system disorders
Rare: thrombocytopenia, leukopenia, agranulocytosis and eosinophilia.
Metabolic
Very common: mainly when using high doses - hypokalemia, hyperuricemia (may lead to exacerbation of gout), increased cholesterol and triglyceride levels in the blood.
Common: hyponatremia, hypomagnesemia, hyperglycemia and glycosuria, worsening of the disease in patients with diabetes mellitus, manifestation of latent diabetes mellitus, increased urea and creatinine levels (especially at the beginning of treatment).
Rare: hypercalcemia.
Very rare: hypochloraemic alkalosis.
From the nervous system
Common: headache, dizziness and weakness.
Rare: paresthesia.
From the organs of vision
Rare: visual impairment, decreased tear production.
Cardiovascular system
Common: hypotension, orthostatic hypotension, palpitations.
Rare: cardiac arrhythmia.
Respiratory, thoracic and mediastinal disorders
Very rare: idiosyncratic (allergic) pulmonary edema, difficulty breathing.
Gastrointestinal tract
Common: loss of appetite, dry mouth, minor gastrointestinal disturbances, nausea, vomiting, upper abdominal pain and cramps, constipation and diarrhoea.
Very rare: pancreatitis.
Hepatobiliary system
Rare: intrahepatic cholestasis or jaundice.
Skin and subcutaneous tissue disorders
Common: urticaria and other forms of skin rashes, itching.
Rare: photosensitivity, allergic vasculitis.
Musculoskeletal and connective tissue disorders
Common: muscle hypotension, muscle cramps.
Kidney and urinary system disorders
Very rare: allergic interstitial nephritis.
Reproductive system and breast disorders
Common: impotence
Reporting of adverse reactions
Reporting of suspected adverse reactions after the authorisation of a medicinal product is important. It allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Expiration date
2 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister, 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyivmedpreparat".
Location of the manufacturer and its business address
Ukraine, 01032, Kyiv, Saksaganskoho St., 139.
